The basic postulate of these studies is that central and peripheral chemoreceptor inputs alone have not provided adequate explanations for many experimental and clinical findings involving the control of breathing. The long-range hypothesis is that neural input to and neural mechanisms within the respiratory control system are more important than traditionally believed. The rationale for the approach used in the studies is that ventilation, often used as the output variable, is a number of information steps removed from neural output itself, and that the system is a closed servo-loop. These studies use various neural respiratory outputs (e.g. phrenic n.) in paralyzed animals, thereby allowing use of "open-loop" experimental conditions that avoid the negative chemical feedback associated with changes of ventilation. Other neural feedback loops can also be opened so unmodified input-output relations can be studied. All studies are performed in anesthetized, decerebrate or decorticate animals. Specific aims are to study: 1) split-brainstem preparations in anesthetized animals with emphasis on interactions of independent medullary and phrenic rhythms; 2) the neural respiratory, sympathetic and other effects of penicillin-induced cortical seizure activity in anesthetized animals; 3) the brainstem mechanism that leads to a respiratory afterdischarge, or "memory", by looking at activity of tonic medullary neurons and by measuring K+ concentration in the medulla during the afterdischarge process; 4) respiratory interactions between the locomotory hypothalamic central command mechanism and other peripheral inputs, and to demonstrate possible involvement of intermediate areas of the ventral medulla in the respiratory and circulatory responses to the central command signal; 5) respiratory effects of reversible cooling of the hypothalamis and midbrain; 6) the effects of hypoxia on medullary ECF pH and respiration, with emphasis on the adenosine-mediated components of the responses; 7) the topology of resetting of respiratory rhythm. The findings should lead to better understanding of control mechanisms involved in resting and exertional breathing and therefore to a better understanding of abnormalities in clinical disease states and of potential ways to treat them.